2-Methoxyestradiol, once considered an inacitve end-metabolite of estradiol, has recently emerged as a very promising agent for cancer treatment. It is orally active in a wide range of tumor models, and inhibits tumor growth at doses showing no clinical signs of toxicity. 2ME2 targets both the tumor cell and endothelial cell compartments by inducing apoptosis in rapidly proliferating cells and inhibiting blood vessel formation at several stages in the angiogenic cascade. Moreover, the ability of 2ME2 to inhibit metastatic spread in several models adds to its therapeutic value for cancer treatment at various stages of the disease. Though the mechanism of action is still undefined, several potential molecular targets and pathways of activation have been suggested.